Corticotropin-Releasing Factor: Pharmacokinetics in Man

Corticotropin-releasing factor (CRF)a 41-amino acid peptide isolated and sequenced from ovine hypothalami, has potential clinical application as a provocative test of the hypothalamic-pituitary-adrenal axis. To define its pharmacokinetic parameters in man, we measured the MCR and plasma half-life of immunoreactive CRF (IR-CRF) by the pulse injection and continuous infusion methods. Synthetic ovine CRF was given to 12 normal men as a bolus injection (1 µg/kg; n = 6) or as a continuous infusion (0.51 ± 0.05 µg/kg-h; n = 6) over 8 h. The disappearance curve of IR-CRF from plasma was biexponential. The plasma half-life of IR-CRF was 11.6 ± 1.5 min (mean ± SE) for the fast component and 73 ± 8 min for the slow component. The MCR using the pulse injection technique was 95 ± 11 liters/m² -day, and the volume of distribution was 6.2 ± 0.5 liters. Continuous infusion of CRF gave approximately the same MCR (88 ± 7 liters/m² day). A small percentage of IR-CRF (∼0.03%) was found in the urine at the end of the continuous infusion. The relatively low MCR of CRF may explain its prolonged biological action in primates and man.